https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51575 Wed 29 May 2024 15:12:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45089 Wed 26 Oct 2022 14:04:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45117 Wed 26 Oct 2022 12:45:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45003 n = 19), including 7 with NEA and healthy controls (n = 10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50 μg/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array. Results: Baseline efferocytosis (mean (±standard deviation)) was lower in participants with asthma (33.2 (±17.7)%) compared with healthy controls (45.3 (±15.9)%; p = 0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (±19.2)%) and NEA (28.7 (±21.5)%; p = 0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (±18.1)%) compared with baseline (30.4 (±19.7)%; p = 0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r = − 0.671; p = 0.017). Galectin-3 was diffusely distributed in most MDMs but formed punctate structures in 5% of MDMs. MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p = 0.044) while IL-6 and CXCL8 levels were similar. Conclusions: Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.]]> Wed 26 Oct 2022 09:42:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31068 Wed 24 Nov 2021 15:51:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46450 Wed 23 Nov 2022 14:17:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28095 Wed 22 Mar 2023 16:25:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51839 Wed 20 Sep 2023 16:12:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54877 Wed 20 Mar 2024 13:18:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37130 Wed 19 Aug 2020 12:59:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21992 Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1β, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Conclusion: Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.]]> Wed 17 Nov 2021 16:31:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36834 Wed 17 Nov 2021 16:29:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24377 1.5 fold in subjects with asthma, whereas, in healthy controls, only 14 entities were differentially expressed. Of the 168 genes that were changed in asthma, several biological processes were overrepresented, with 25 genes involved in "immune system processes". qPCR confirmed that S100P, S100A16, MAL and MUC1 were significantly increased in the asthma group post-meal. We also observed a strong correlation and a moderate correlation between the change in NLRP12 and S100A16 gene expression at 4 h compared to baseline, and the change in total and saturated non-esterified plasma fatty acid levels at 2 h compared to baseline. In summary, our data identifies differences in inflammatory gene expression that may contribute to increased airway neutrophilia following a high fat meal in subjects with asthma and may provide useful therapeutic targets for immunomodulation. This may be particularly relevant to obese asthmatics, who are habitually consuming diets with a high fat content.]]> Wed 17 Nov 2021 16:29:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38604 a production in a dose-dependent manner with a decrease in cell viability at higher doses. Although treatment with CGA alone had no effect on TNF-a production, it however enhanced cell viability and co-administration with curcumin at a 1:1 ratio caused a synergistic reduction in TNF-a production with no impact on cell viability. Furthermore, an qRT-PCR analysis of NF-KB pathway components and inflammatory biomarkers indicated that CGA alone was not effective in reducing the mRNA expression of any of the tested inflammatory marker genes, except TLR-4. However, co-administration of CGA with curcumin, potentiated the anti-inflammatory effects of curcumin. Curcumin and CGA together reduced the mRNA expression of pro-inflammatory cytokines [TNF-a (~88%) and IL-6 (~99%)], and COX-2 (~92%), possibly by suppression of NF-KB (~78%), IKB-β-kinase (~60%) and TLR-4 receptor (~72%) at the mRNA level. Overall, co-administration with CGA improved the inflammation-lowering effects of curcumin in THP-1 cells.]]> Wed 17 Nov 2021 15:41:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47176 Wed 14 Dec 2022 15:55:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40650 Wed 13 Mar 2024 08:56:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16761 Wed 11 Apr 2018 16:55:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29666 10 mg/L, or who were taking anti-inflammatory medications or n-3PUFA supplements, 126 participants (age 77.6 ± 7.3 years; females, 46%) were included in the analysis. After multivariate adjustments, O3I was inversely associated with CRP (β = −0.209, p < 0.05) and monocyte cell counts (β = −0.205, p < 0.05), and total n-3PUFA was inversely related to WBC (β = −0.238, p < 0.05), neutrophils (β = −0.212, p < 0.05) and monocytes (β = −0.246, p < 0.05). However no association between fibrinogen and O3I or total n-3PUFA was detected. Conclusions: This study demonstrated a negative association between O3I and biomarkers of inflammation in an older population. The findings support a potential role for n-3PUFA supplementation in the management of inflammatory diseases.]]> Wed 11 Apr 2018 16:52:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14161 Wed 11 Apr 2018 16:03:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21250 n = 99) and healthy controls (n = 61) were recruited. Blood was collected and spirometry was performed. The DII was calculated from food frequency questionnaires administered to study subjects. Results: The mean DII score for the asthmatics was higher than the mean DII score for healthy controls (- 1.40 vs. - 1.86, P = 0.04), indicating that their diets were more pro-inflammatory. For every 1 unit increase in DII score, the odds of having asthma increased by 70% (OR: 1.70, 95% CI: 1.03, 2.14; P = 0.040). FEV₁ was significantly associated with DII score (ß = - 3.44, 95% CI: - 6.50, - 0.39; P = 0.020), indicating that for every 1 unit increase in DII score, FEV₁ decreased by 3.44 times. Furthermore, plasma IL-6 concentrations were positively associated with DII score (ß = 0.13, 95% CI: 0.05, 0.21; P = 0.002). Conclusion and Clinical Relevance: As assessed using the DII score, the usual diet consumed by asthmatics in this study was pro-inflammatory relative to the diet consumed by the healthy controls. The DII score was associated with increased systemic inflammation and lower lung function. Hence, consumption of pro-inflammatory foods may contribute to worse asthma status, and targeting an improvement in DII in asthmatics, as an indicator of suitable dietary intake, might be a useful strategy for improving clinical outcomes in the disease.]]> Wed 11 Apr 2018 15:08:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28327 in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the anti-inflammatory protein – tristetraprolin (TTP), a destabilizing RNA binding protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition increases TTP mRNA expression, resultant TTP protein builds up in the hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro-inflammatory cytokines increase and anti-inflammatory proteins are rendered inactive. Importantly, these effects can be reversed by the PP2A activators FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression in cells stimulated with TNFα; as inhibition of PP2A with OA or PP2A-C siRNA results in significant increases in cytokine production. Collectively, these data reveal the molecular mechanisms of PP2A regulation and highlight the potential of boosting the power of endogenous phosphatases as novel anti-inflammatory strategies to combat asthmatic inflammation.]]> Wed 11 Apr 2018 13:50:35 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:6954 Wed 11 Apr 2018 13:48:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14519 Wed 11 Apr 2018 13:27:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22609 Wed 11 Apr 2018 13:07:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15695 Wed 11 Apr 2018 12:28:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22884 vs. a nut free diet on adiposity and cardio-metabolic risk markers. In a randomised cross-over design, 61 healthy subjects (65 ± 7 years, body mass index (BMI) 31 ± 4 kg/m²) alternated either high oleic peanuts (15%-20% of energy) or a nut free diet for 12 weeks. Body composition and mass, waist circumference, C-reactive protein (CRP), lipids, glucose and insulin were assessed at baseline and after each phase. Repeated measures analysis of variance (ANOVA) compared the two diets. Consistent with other nut studies, there were no differences in lipids, CRP, glucose and insulin with peanut consumption. In contrast, some reports have demonstrated benefits, likely due to differences in the study cohort. Energy intake was 10% higher (853 kJ, p < 0.05), following peanut consumption vs. control, attributed to a 30% increase in fat intake (p < 0.001), predominantly monounsaturated (increase 22 g, p < 0.05). Despite greater energy intake during the peanut phase, there were no differences in body composition, and less than predicted increase (0.5 kg) in body weight for this additional energy intake, possibly due to incomplete nutrient absorption and energy utilisation.]]> Wed 11 Apr 2018 11:43:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29130 Wed 11 Apr 2018 10:45:46 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19199 Wed 11 Apr 2018 10:44:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14158 Wed 11 Apr 2018 10:28:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30136 Wed 10 Nov 2021 15:14:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34558 Wed 10 Nov 2021 15:14:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35136 Wed 10 Nov 2021 15:04:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48668 Wed 06 Mar 2024 14:27:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41407 Wed 03 Aug 2022 11:03:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49012 Wed 01 May 2024 15:54:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13830 Tue 24 Aug 2021 14:29:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21812 n = 131) were recruited as part of a longitudinal study while attending antenatal care clinics during pregnancy; blood samples were collected up to three times in pregnancy. Serum cotinine, indicating exposure to cigarette smoke, was detected in 50.4% of mothers. Compared with non-Indigenous women, the cohort had 10 times the prevalence of antibodies to Helicobacter pylori (33 vs. 3%). Levels of immunoglobulin G, antibodies to H. pylori, and C-reactive protein (CRP) were all inversely correlated with gestational age (P < 0.05). CRP levels were positively associated with maternal body mass index (BMI; ρ = 0.449, P = 0.001). The effects of cigarette smoke (cotinine) and inflammation (CRP) were assessed in relation to risk factors for SIDS: gestational age at delivery and birth weight. Serum cotinine levels were negatively associated with birth weight (ρ = -0.37, P < 0.001), this correlation held true for both male (ρ = -0.39, P = 0.002) and female (ρ = -0.30, P = 0.017) infants. Cotinine was negatively associated with gestational age at delivery (ρ = -0.199, P = 0.023). When assessed by fetal sex, this was significant only for males (ρ = -0.327, P = 0.011). CRP was negatively associated with gestational age at delivery for female infants (ρ = -0.46, P < 0.001). In contrast, maternal BMI was significantly correlated with birth weight. These data highlight the importance of putting programs in place to reduce cigarette smoke exposure in pregnancy and to treat women with chronic infections such as H. pylori to improve pregnancy outcomes and decrease risk factors for sudden death in infancy.]]> Tue 24 Apr 2018 16:00:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54347 Tue 20 Feb 2024 16:20:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46307 Alternaria Alternata (AA)– induced airway inflammation. Methods: PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published a7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-kB were also determined. Results: PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-kB phosphorylation in the PNU-282987–treated group when compared to the GTS-21–treated ILC2s. Conclusion: PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.]]> Tue 15 Nov 2022 10:22:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45541 2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. Conclusion: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. Clinical trial registration: ACTRN12616000732482p.]]> Tue 14 Nov 2023 14:41:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51613 Tue 12 Sep 2023 13:49:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32053 Tue 03 Sep 2019 17:54:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30397 Tue 01 May 2018 09:18:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36051 Thu 28 Oct 2021 13:04:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23093 Thu 28 Oct 2021 13:04:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33793 –/–) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild‐type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c^–/– mice with AAD also had reduced numbers of α‐smooth muscle actin‐positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)‐5, IL‐13, IL‐33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL‐5, IL‐33 and TNF levels in lung‐draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3‐positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL‐5 and IL‐13 from co‐cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium‐treated controls. Our data show that Fbln1c may be a therapeutic target in chronic asthma.]]> Thu 28 Oct 2021 13:02:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45028 Zfp36 gene is an anti‐inflammatory protein that induces mRNA decay, especially of transcripts encoding inflammatory cytokines, including those implicated in COPD. Methods: Here, we identify a novel protective role for TTP in CS‐induced experimental COPD using Zfp36^aa/aa mice, a genetically modified mouse strain in which endogenous TTP cannot be phosphorylated, rendering it constitutively active as an mRNA‐destabilising factor. TTP wild‐type (Zfp36^+/+) and Zfp36^aa/aa active C57BL/6J mice were exposed to CS for four days or eight weeks, and the impact on acute inflammatory responses or chronic features of COPD, respectively, was assessed. Results: After four days of CS exposure, Zfp36^aa/aa mice had reduced numbers of airway neutrophils and lymphocytes and mRNA expression levels of cytokines compared to wild‐type controls. After eight weeks, Zfp36^aa/aa mice had reduced pulmonary inflammation, airway remodelling and emphysema‐like alveolar enlargement, and lung function was improved. We then used pharmacological treatments in vivo (protein phosphatase 2A activator, AAL_(S), and the proteasome inhibitor, bortezomib) to promote the activation and stabilisation of TTP and show that hallmark features of CS‐induced experimental COPD were ameliorated. Conclusion: Collectively, our study provides the first evidence for the therapeutic potential of inducing TTP as a treatment for COPD.]]> Thu 27 Oct 2022 09:28:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:594 99%) was inactivated (and bound to tissue inhibitor of metalloproteinase-1). In neutrophilic asthma, more subjects had NE activity (39%) compared with both healthy control subjects (0%), subjects with eosinophilic asthma (6%), or subjects with paucigranulocytic asthma (0%, p < 0.05). There were strong and consistent positive correlations between interleukin-8, neutrophils, and proteolytic enzymes. MMP-9 was inversely correlated with NE (r = -0.93). Conclusions: Proteolytic enzyme activity in asthma is dependent on the underlying inflammatory phenotype and is differentially regulated with MMP-9 activity a feature of eosinophilic inflammation, and active NE in neutrophilic inflammation.]]> Thu 25 Jul 2013 09:10:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:660 Thu 25 Jul 2013 09:10:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50862 Thu 17 Aug 2023 11:36:01 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44508 Thu 16 May 2024 08:36:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34467 -1.min^-1) underwent a clinical evaluation of known risk factors by a physician and comprehensive laboratory analysis of immune responses both at rest and after two cycling ergometer tests: 60 min at 65% VO₂max (LONG); and 6 x 3 min intervals at 90% VO₂max (INTENSE). Blood tests were performed to determine Epstein Barr virus (EBV) status and DNA was genotyped for a panel of cytokine gene polymorphisms. Saliva was collected for measurement of IgA and detection of EBV DNA. Athletes were then followed for 9 months for self-reported episodes of respiratory illness, with confirmation of the underlying cause by a sports physician. There were no associations with risk of respiratory illness identified for any parameter assessed in the clinical evaluations. The laboratory parameters associated with an increased risk of respiratory illnesses in highly-trained athletes were cytokine gene polymorphisms for the high expression of IL-6 and IFN-γ expression of EBV-DNA in saliva; and low levels of salivary IgA concentration. A genetic risk score was developed for the cumulative number of minor alleles for the cytokines evaluated. Athletes prone to recurrent respiratory illness were more likely to have immune disturbances that allow viral reactivation, and a genetic predisposition to pro-inflammatory cytokine responses to intense exercise.]]> Thu 14 Mar 2019 16:50:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7725 Sat 24 Mar 2018 10:48:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4601 Sat 24 Mar 2018 10:13:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7396 Sat 24 Mar 2018 08:42:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8243 3.0 mg/l). Body composition and anthropometric measurements were recorded. Hs-CRP was analysed using immunoassays and fatty acids were measured by gas chromatography. Plasma hs-CRP concentration was negatively correlated with total n-3 fatty acids (P=0.05), eicosapentaenoic acid (EPA; P=0.002) and docosapentaenoic acid (DPA; P=0.01). The highest hs-CRP tertile (>3.0 mg/l) had significantly lower concentrations of total n-3 fatty acids, EPA and DPA, when compared with the other tertiles (P<0.05). This study provides evidence that in healthy individuals, plasma n-3 fatty acid concentration is inversely related to hs-CRP concentration, a surrogate marker of CVD risk.]]> Sat 24 Mar 2018 08:40:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9675 Sat 24 Mar 2018 08:39:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1628 99%) was inactivated (and bound to tissue inhibitor of metalloproteinase-1). In neutrophilic asthma, more subjects had NE activity (39%) compared with both healthy control subjects (0%), subjects with eosinophilic asthma (6%), or subjects with paucigranulocytic asthma (0%, p < 0.05). There were strong and consistent positive correlations between interleukin-8, neutrophils, and proteolytic enzymes. MMP-9 was inversely correlated with NE (r = –0.93). Conclusions: Proteolytic enzyme activity in asthma is dependent on the underlying inflammatory phenotype and is differentially regulated with MMP-9 activity a feature of eosinophilic inflammation, and active NE in neutrophilic inflammation.]]> Sat 24 Mar 2018 08:30:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13283 Sat 24 Mar 2018 08:15:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10899 Sat 24 Mar 2018 08:09:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17478 −/−-deficient mice. In the caput epididymis of Ido1^−/− animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal.]]> Sat 24 Mar 2018 08:04:10 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19925 Sat 24 Mar 2018 08:03:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19926 Sat 24 Mar 2018 08:03:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20744 2t concentration were assessed. The experimental procedure was repeated with the remaining supplement after a 3-wk washout. Eight participants completed both supplementation trials. Results: NAC improved sprint performance during the cycle ergometer race simulation (P < 0.001, η_p² = 0.03). Supplementation with NAC also augmented postexercise plasma total antioxidant capacity (P = 0.005, η_p² = 0.19), reduced exercise-induced oxidative damage (plasma thiobarbituric acid-reactive substances, P = 0.002, η_p² = 0.22; urinary 15-isoprostane F_2t concentration, P = 0.010, η_p² = 0.431), attenuated inflammation (plasma interleukin 6, P = 0.002, η_p² = 0.22; monocyte chemotactic protein 1, P = 0.012, η_p² = 0.17), and increased postexercise nuclear factor κB activity (P < 0.001, η_p² = 0.21). Conclusion: Oral NAC supplementation improved cycling performance via an improved redox balance and promoted adaptive processes in well-trained athletes undergoing strenuous physical training.]]> Sat 24 Mar 2018 08:00:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18941 Sat 24 Mar 2018 07:58:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16896 Sat 24 Mar 2018 07:58:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21125 Sat 24 Mar 2018 07:53:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21041 Sat 24 Mar 2018 07:50:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:6787 Sat 24 Mar 2018 07:46:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26880 -8). Limitations, Reasons for Caution: The meta-analysis for moderate-to-severe endometriosis included results of moderate-to-severe endometriosis cases from our European data sets and all endometriosis cases from the Japanese data sets, as disease stage information was not available for endometriosis cases in the Japanese data sets. Wider Implications of the Findings: SNP rs6542095 is located ~2.3 kb downstream of the IL1A gene and ~6.9 kb upstream of cytoskeleton-associated protein 2-like (CKAP2L) gene. The IL1A gene encodes the IL1a protein, a member of the interleukin 1 cytokine family which is involved in various immune responses and inflammatory processes. These results provide important replication in an independent Japanese sample and, for the first time, association of the IL1A locus in endometriosis patients of European ancestry. SNPs within the IL1A locus may regulate other genes, but if IL1A is the target, our results provide supporting evidence for a link between inflammatory responses and the pathogenesis of endometriosis. Study Funding/Competing Interest(s): The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.]]> Sat 24 Mar 2018 07:41:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28879 Sat 24 Mar 2018 07:40:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27390 Sat 24 Mar 2018 07:34:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22024 Sat 24 Mar 2018 07:15:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38861 Streptococcus pneumoniae, mechanistically through inhibition of the antimicrobial peptide (AMP) cathelicidin. Using experiments in human cells and mouse infection models, we performed a head-to-head comparison of the effects of the major ICS agents used in COPD on innate immunity.]]> Mon 29 Jan 2024 17:53:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38260 9-tetrahydrocannabinol (∆⁹-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively. An increasing number of preclinical studies have established that ∆⁹-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking. In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis. Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.]]> Mon 29 Jan 2024 17:45:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38383 Mon 29 Jan 2024 17:45:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48674 Mon 27 Mar 2023 14:11:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33098 Mon 27 Aug 2018 12:12:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36719 Mon 24 Aug 2020 10:45:35 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32745 Mon 23 Sep 2019 14:10:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32782 Mon 23 Sep 2019 14:01:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34885 Mon 23 Sep 2019 11:28:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34174 Mon 23 Sep 2019 10:19:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49546 Mon 22 May 2023 08:45:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51758 Mon 18 Sep 2023 14:22:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47389 Mon 16 Jan 2023 15:45:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45802  94 cm in males, > 80 cm in females) or inflammation (hs-CRP > 1 mg/L). In the subgroup with abdominal obesity, ox-LDL decreased by 13.5 mU/mL (95% CI − 23.5 to − 3.6) and TAC increased by 0.04 mM (95% CI 0.006–0.07) only after HPOO consumption. In the subgroup with inflammation, hs-CRP decreased by 1.9 mg/L (95% CI − 3.7 to −0.1) only in the HPOO arm. Conclusions: Although there were no significant differences between treatments, the changes observed after HPOO consumption demonstrate the antioxidant and anti-inflammatory effect of this oil, which is more pronounced in adults with high cardiometabolic risk (Clinical Trial Registration: ACTRN12618000706279).]]> Mon 07 Nov 2022 10:05:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42832 2 SD 3.9) participated in a crossover, randomized, controlled, double-blind clinical trial (registered under Australian New Zealand Clinical Trials Registry, identifier no. ACTRN12620000437965). Participants consumed a HFHE meal with a 250 mL dose of either intervention (anthocyanins-rich Queen Garnet Plum) or control (apricot) juice. Blood samples and blood pressure measures were collected at baseline, 2 h and 4 h following the HFHE meal. Vascular and microvascular function were evaluated at baseline and 2 h after the HFHE meal. Results: Participants had a higher 2 h postprandial flow-mediated dilatation (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P = 0.019 and P = 0.049, respectively). C-reactive protein was lower 4 h postprandially in the anthocyanins (1.80 mg/L, IQR 0.90) vs control arm (2.30 mg/L, IQR 1.95) (P = 0.026), accompanied by a trend for lower concentrations of interleukin-6 (P = 0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor alpha, interleukin-1 beta, or maximum microvascular perfusion following iontophoresis of acetylcholine. Conclusion: Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat 'Western' meal. Further studies are required to better elucidate the clinical implications of postprandial biomarkers of CVD.]]> Mon 05 Sep 2022 12:31:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37876 Fri 28 May 2021 12:47:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21995 Fri 25 May 2018 17:44:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41076 Fri 22 Jul 2022 17:04:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37059 Fri 21 Aug 2020 11:53:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53126 Fri 17 Nov 2023 12:21:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38377 Fri 10 Sep 2021 12:38:35 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40363 Fri 08 Jul 2022 14:24:38 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53596 Fri 08 Dec 2023 16:00:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44100 –9 and replicated the finding in the validation set (OR 1.48; 95% CI 1.09–1.99; P = .01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32–1.98; P = 4.0 × 10^–6; allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21–1.56; P = 1.5 × 10^–6; allele frequency = 11.5%). Among amoxicillin- and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and DRB1*15:01. Conclusions: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.]]> Fri 07 Oct 2022 14:21:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37039 Fri 07 Aug 2020 12:28:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24548 Fri 03 Dec 2021 10:34:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37118 Fri 03 Dec 2021 10:32:20 AEDT ]]>